CRYSTAL STRUCTURE OF HUMAN RHINOVIRUS 3 AND COMPARISON WITH OTHER RHINOVIRUSES. Rui Zhao, Marcia Kremer, Richard Kuhn, Michael Rossmann, Dept. of Biological Sciences, Purdue University, W. Lafayette, IN 47907, USA, Daniel Pevear, Vincent Giranda, Jennifer Kofron, Mark McKinlay, Former Sterling Winthrop Pharmaceutical Research Division, 1250 S. Collegeville Rd., PO Box 5000, Collegeville, Pennsylvania 19426 0900, USA

Human Rhinovirus (HRV) is the major causative agent of common cold in humans and consists of over 100 different serotypes. These can be roughly divided into a major and minor group according to their cellular receptors. The crystal structures of HRV14 and HRV16, major receptor group rhinoviruses, as well as HRV1A, a minor receptor group rhinovirus, have been previously determined. Sequence comparisons had shown that HRV14 seemed to be an outlyer among rhinoviruses. Furthermore, HRV14 was the only virus with no cellular "pocket factor" in a hydrophobic pocket thought to regulate viral stability. The structure of HRV3, another major receptor group virus, was determined by the Molecular Replacement method. The amino acid sequence of HRV3 capsid proteins was obtained through cDNA cloning of the HRV3 RNA genome. Suprisingly, the structure and amino acid sequence of HRV3 are very similar to HRV14. Like HRV14, it also had no bound "pocket factor". A structural basis for the different antigenic and stability properties displayed by HRV3 has been proposed, and the implications of the similarity between HRV3 and HRV14 will be discussed.

There is non-protein electron density on the vital five-fold axes of all known rhinovirus crystal structures. Difference electron density maps between EGTA-soaked crystals of HRV14 as well as HRV16, and their corresponding native structures show that this density is a EGTA-chelatable ion. Analysis of the coordination geometry indicates that the ions in HRV3, HRV14 and HRV1A are likely to be Ca⁺⁺, and the ion in HRV16 could be Zn⁺⁺. These cations may play a role in regulation of the rhinovirus stability, although the loss of the ion itself seems not enough to lead to viral disassembly.